ABSTRACT
Aim To establish and optimize a method for screening HIV-1 integrase 3′-processing inhibitor. Methods Fluorescence resonance energy transfer ( FRET) was used to create an assay for screening in-tegrase 3′-processing inhibitors; wavelength was de-fined by DNaseⅠ; factors affecting IN activity were optimized, including buffer composition, substrate con-centration, enzyme concentration, metal ion concentra-tion. Results Integrase 3′-processing optimizing reac-tion conditions were buffer 1 , 500 nmol · L-1 sub-strate, 1 μmol·L-1 integrase, 20mmol·L-1 magne-sium ion. Positive drug raltegravir and myricetin could effectively inhibit integrase 3′-processing activity using this assay. Two integrase 3′-processing inhibitors were screened by this method. Conclusion The method for screening HIV-1 integrase 3′-processing inhibitor is successfully established and optimized.
ABSTRACT
Human epidermal growth factor receptor 2 (HER2) belongs to the transmembrane glycoprotein receptor family. Overexpression of HER2 could directly lead to tumorigenesis and metastasis. This phenomenon could be observed in the breast cancer, ovarian cancer, gastric cancer, lung cancer and prostate cancer. Compared with the conventional chemotherapy, the targeted treatment of antibody is more specific and has lower side effects. This review describes the current status of monotherapy and combination therapies of anti-HER2 antibodies, trastuzumab and pertuzumab, with chemotherapeutic drugs. The development trends of new formats of anti-HER2 antibody drugs such as bispecific antibody, immunotoxin are also discussed.
ABSTRACT
Monoclonal antibody-targeted therapy has been a hot spot in current clinical cancer treatment. As current antibody drugs have large molecule sizes leading to poor tissue penetration, and high dosage in clinical application leading to high cost, to overcome the problems, the development of new antibody drugs with miniaturization and high potency has become a new trend. In recent years, the conjugates of monoclonal antibodies and cytotoxins, called antibody-drug conjugates (ADCs), have entered the arsenal of anti-cancer drugs, becoming a new format of antibody drugs and attracting extensive attentions. The ADC molecule usually consists of antibody, linker and effector molecule. According to different effector molecules, ADCs can be divided into three categories as chemo-conjugates, immunotoxins and radio-conjugates. When ADC molecules are internalized into cancer cells, cytotoxins will be released by chemical, enzyme degradation or by action of lysosomal proteases, then kill targeted cells by inhibiting protein synthesis, depolymerizing microtubules or breaking double-strand DNA. Recently, two ADC drugs have been approved by the US FDA and more ADC drug candidates are in clinical phase II or III trials which show significantly clinical effects and attracting much attention and competition of pharmaceutical enterprises. In this review, antibody conjugates in the past and present will be summarized and the future development trends and challenges of this type of antibody drugs will be discussed.
ABSTRACT
Integration is a critical step in the retroviral life cycle.HIV-1 integrase is involved in the integration of HIV DNA into host chromosomal DNA and appears to have no functionally equivalent in human cells.It has become an attractive and rational target for selective anti-AIDS therapy.A random linear heptapeptides phage display library was panned on the recombinant HIV-1 integrase protein.After five rounds of panning,13 positive phage clones were selected and sequenced.Two consensus peptides(TPSHSSR and HPERATL) were chemically synthesized.The non-radioactive ELISA-based HIV-1 integrase assay showed that the synthetic peptides TPSHSSR and HPERATL were able to inhibit the 3'cleavage or strand transfer activity of HIV-1 integrase to some extent(IC50=(54.56?5.18) ?mol/L,IC50=(28.29?1.32) ?mol/L,respectively) .These heptapeptides could be used for developing new anti-HIV drug candidates,as well as for structural studies of the three-dimensional structure of the entire integrase molecule.
ABSTRACT
Phage display is a new technology developed in recent years. Random peptides displayed on the filamentous phage surface offer a rich source of molecular diversity in searching for ligands that bind an antibody, receptor and other proteins. The phage display system has been effective in the discovery of various ligands. Potential applications of the peptide library include investigation of the protein protein interactions and discovery of mimetic drug candidates.